BRIAN SMITH

Brian C. Smith, Ph.D.
Associate Professor of Biochemistry
Associate Director, Program in Chemical Biology
Associate Director, Structural Genomics Unit, Mellowes Center for Genomic Sciences & Precision Medicine
brismith@mcw.edu
414-955-5669

EDUCATION AND TRAINING

B.S. 2003, Chemistry University of Illinois at Urbana-Champaign

Ph.D. 2008, Organic Chemistry, Laboratory of John Denu, University of Wisconsin-Madison

Postdoc, 2009-2014, Nitric Oxide Signaling, Laboratory of Michael Marletta, University of California-Berkeley and Scripps Research Institute

PUBLICATIONS

Smith Lab Publications
(Lab personnel bolded)

53. Shishodia S, Nunez R, Stormier BP, Bursch KL, Goetz CJ, Olp MD, Jensen DR, Fenske TG, Ordonez-Rubiano SC, Blau ME, Roach MK, Peterson FC, Volkman BF, Dykhuizen EC, Smith BC. Selective and Cell-Active PBRM1 Bromodomain Inhibitors Discovered through NMR Fragment Screening. Journal of Medicinal Chemistry. 2022 October. doi: 10.1021/acs.jmedchem.2c00864

52. Stodola TJ, Chi YI, De Assuncao TM, Leverence EN, Tripathi S, Dsouza NR, Mathison AJ, Volkman BF, Smith BC, Lomberk G, Zimmermann MT, Urrutia R. Computational modeling reveals key molecular properties and dynamic behavior of disruptor of telomeric silencing 1-like (DOT1L) and partnering complexes involved in leukemogenesis. Proteins. 2022 Jan;90(1):282-298. doi: 10.1002/prot.26219. Epub 2021 Sep 12. PubMed PMID: 34414607; PubMed Central PMCID: PMC8671179.

51. Chi YI, Stodola TJ, De Assuncao TM, Leverence EN, Smith BC, Volkman BF, Mathison AJ, Lomberk G, Zimmermann MT, Urrutia R. Structural bioinformatics enhances the interpretation of somatic mutations in KDM6A found in human cancers. Comput Struct Biotechnol J. 2022;20:2200-2211. doi: 10.1016/j.csbj.2022.04.028. eCollection 2022. PubMed PMID: 35615018; PubMed Central PMCID: PMC9111933.

50. Nord JA, Wynia-Smith SL, Gehant AL, Jones Lipinski RA, Naatz A, Rioja I, Kumar Prinja R, Corbett JA, Smith BC. N-terminal BET bromodomain inhibitors disrupt a BRD4-p65 interaction and reduce inducible nitric oxide synthase transcription in pancreatic ß-cells. Frontiers in Endocrinology. 2022. DOI: 10.3389/fendo.2022.923925.

49. Fisher CL, Fallot LB, Wan TC, Keyes RF, Suresh RR, Rothwell AC, Gao ZG, McCorvy JD, Smith BC, Jacobson KA, Auchampach JA. Characterization of Dual-Acting A3 Adenosine Receptor Positive Allosteric Modulators That Preferentially Enhance Adenosine-Induced Gαi3 and GαoA Isoprotein Activation. ACS Pharmacol Transl Sci. 2022 Aug 12;5(8):625-641. doi: 10.1021/acsptsci.2c00076. eCollection 2022 Aug 12. PubMed PMID: 35983277; PubMed Central PMCID: PMC9380209.

48. Johnston N, Samuels TL, Goetz CJ, Arnold LA, Smith BC, Seabloom D, Wuertz B, Ondrey F, Wiedmann TS, Vuksanovic N, Silvaggi NR, MacKinnon AC, Miller J, Bock J, Blumin JH. Oral and Inhaled Fosamprenavir Reverses Pepsin-Induced Damage in a Laryngopharyngeal Reflux Mouse Model. Laryngoscope. 2022 Jun 9;. doi: 10.1002/lary.30242. PubMed PMID: 35678265; NIHMSID:NIHMS1811733.

47. Kanack AJ, Olp MD, Newsom OJ, Scaglione JB, Gooden DM, McMahon K, Smith BC, Scaglione K. Chemical regulation of the protein quality control E3 ubiquitin ligase C-terminus of Hsc70 interacting protein (CHIP)ChemBioChem. 2022. DOI: 10.1002/cbic.202100633. PMID 35061295.

46. Kalous KS, Wynia-Smith SL, Smith BC. Sirtuin oxidative post-translational modificationsFront Physiol. 2021. DOI:10.3389/fphys.2021.763417 PMID: 34899389. PMCID: PMC8652059

    45. Sprague DJ, Getschman AE, Fenske TG, Volkman FB, Smith BC. Trisubstituted 1,3,5-Triazines: The First Ligands of the sY12-Binding Pocket on Chemokine CXCL12. ACS Med Chem Lett. 2021. DOI: 10.1021/acsmedchemlett.1c00388.

    44. Chi YI, Stodola TJ, De Assuncao TM, Levrence EN, Tripathi S, Dsouza NR, Mathison AJ, Basel DG, Volkman BF, Smith BC, Lomberk G, Zimmermann MT, Urrutia R. Molecular mechanics and dynamic simulations of well-known Kabuki syndrome-associated KDM6A variants reveal putative mechanisms of dysfunction. Orphanet J Rare Dis. 2021 Feb 5;16(1):66. doi: 10.1186/s13023-021-01692-w. PubMed PMID: 33546721; PMCID: PMC7866879.

    43. Jones Lipinski RA, Thillier Y, Morisseau C, Sebastiano Jr CS, Smith BC, Hall CD, Katritzky AR. Molecular docking-guided synthesis of NSAID-glucosamine bioconjugates and their evaluation as COX-1/COX-2 inhibitors with potentially reduced gastric toxicityChem Biol Drug Des. 2021:00, 1-12.

    42. Olp MD, Cui H, Pomerantz WC, Smith BC. "Pharmacological Regulation and Functional Significance of Chromatin Binding by BET Tandem Bromodomains." In: Protein-Protein Interaction Regulators. Roy S, Fu H, editors. Cambridge, UK: Royal Society of Chemistry; 2021. Chapter 9; p.209-248.

    41. Goetz CJ, Sprague DJ, Smith BC. "Development of activity-based probes for the protein deacylase Sirt1." Bioorganic Chemistry. 2020, 104:104232. PMID: 32911193.

    40. Yang M, Li W, Harberg C, Chen W, Yue H, Ferreira RB, Wynia-Smith SL, Carroll KS, Zielonka J, Flaumenhaft R, Silverstein RL, Smith BC. "Cysteine sulfenylation by CD36 signaling promotes arterial thrombosis in dyslipidemia." Blood Advances. 2020, 22;4(18):4494-4507. PMCID: PMC7509873.

    39. Olp MD, Kalous KS, Smith BC. "ICEKAT : an interactive online tool for calculating initial rates from continuous enzyme kinetic traces." BMC Bioinformatics. 2020, 21:286. doi: 10.1186/s12859-020-3513-y.

    38. Kalous KS, Wynia-Smith SL, Summers SB, Smith BC. "Human sirtuins are differentially sensitive to nitrosating agents and other cysteine oxidants." Journal of Biological Chemistry. 2020 [epub ahead of print] doi: . PMID 32371394

    37. Kapoor A, Ghosh A, Forman M, Hu X, Ye W, Southall N, Marugan J, Keyes RF, Smith BC, Meyers DJ, Ferrer M, Arav-Boger R. “Validation and Characterization of Five Distinct Novel Inhibitors of Human Cytomegalovirus.” Journal of Medicinal Chemistry. 2020 Mar 27. PMID 32191456. 

    36. Olp MD, Sprague DJ, Goetz CJ, Kathman SG, Wynia-Smith SL, Shishodia S, Summers SB, Xu Z, Statsyuk AV, Smith BC. “Covalent-Fragment Screening of BRD4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites.” ACS Chemical Biology. 2020 March 23. PMID 32149490. 

    35. McCusker P, Mian MY, Li G, Olp MD, Tiruveedhula VVNPB, Rashid F, Golani LK, Verma RS, Smith BC, Cook JM, Chan JD. "Non-sedating benzodiazepines cause paralysis and tissue damage in the parasitic blood fluke Schistosoma mansoni." PLoS Neglected Tropical Diseases. 2019 Nov 15;13(11):e0007826. PMID: 31730614.

    34. Chen Y, Yang M, Huang W, Chen W, Zhao Y, Schulte ML, Volberding PJ, Gerbec Z, Zimmermann MT, Zeighami A, Demos W, Zhang J, Knaack DA, Smith BC, Cui W, Malarkannan S, Sodhi K, Shapiro JI, Xie Z, Sahoo D, Silverstein RL. "Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses." Circulation Research. 2019 Dec 6;125(12):1087-1102. PMID : 31625810.

    33. Hanson QM, Carley JR, Gilbreath TJ, Smith BC, Underbakke ES. “Calmodulin-induced Conformational Control and Allostery Underlying Neuronal Nitric Oxide Synthase Activation”. Journal of Molecular Biology. 2018, 430, 935-47.

    32. Fahey JM, Stancill JS, Smith BC, Girotti AW. “Antagonistic effects of nitric oxide in a glioblastoma photodynamic therapy model: mitigation by BET bromodomain inhibitor JQ1”. Journal of Biological Chemistry. 2018, 293, 5345-59.

    31. Egner JM, Jensen DR, Olp MD, Kennedy NW, Volkman BF, Peterson FC, Smith BC, Hill RB. “Development and Validation of 2D Difference Intensity Analysis for Chemical Library Screening by Protein-Detected NMR Spectroscopy”. ChemBioChem. 2017, 19, 448-58. Appeared as the Cover Article

    30. Olp MD, Zhu N, Smith BC. “Metabolically Derived Lysine Acylations and Neighboring Modifications Tune the Binding of the BET Bromodomains to Histone H4”. Biochemistry. 2017, 56, 5485-5495.

    29. Wynia-Smith SL, Smith BC. “Nitrosothiol formation and S-nitrosation signaling through nitric oxide synthases”. Nitric Oxide. 2017, 63, 52-60.

    28. Kalous KS, Wynia-Smith SL, Olp MD, Smith BC. “Mechanism of Sirt1 NAD+-dependent Deacetylase Inhibition by Cysteine S-nitrosation”. Journal of Biological Chemistry. 2016, 291, 25398-410.

    27. Zhou Y, Wynia-Smith SL, Couvertier, SM, Kalous KS, Marletta MA, Smith BC*, Weerapana E. “Chemoproteomic Strategy to Quantitatively Monitor Transnitrosation Uncovers Functionally Relevant S-Nitrosation Sites on Cathepsin D and HADH2”. Cell Chemical Biology. 2016, 23, 727-37. *Co-corresponding author.

    26Shteyer E and Smith BC. “Tail Tale: nNOS(del1203-1434) Predicts Global Defects in Esophagogastrointestinal Transit Reply”. Gastroenterology. 2015, 149, 261-2.

    25. Shteyer E, Edvardson S, Wynia-Smith SL, Pierri CL, Zangen T, Hashavya S, Begin M, Yaacov B, Cinamon Y, Koplewitz BZ, Vromen A, Elpeleg O, Smith BC. “Truncating Mutation in the Nitric Oxide Synthase 1 Gene Is Associated with Infantile Achalasia”. Gastroenterology. 2015, 148, 533-536.


    Postdoctoral

    24. Bruegger JJ, Smith BC, Wynia-Smith SL, Marletta MA. “Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes”. Journal of Biological Chemistry. 2018, 293, 6282-96.

    23. Rao M, Smith BC, Marletta MA. “Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain TrichCH4B”. MBio. 2015, 6, e00206-15.

    22. Campbell MG, Smith BC, Potter CS, Carragher B, Marletta MA. “The molecular architecture of mammalian nitric oxide synthases”. Proceedings of the National Academy of Sciences. 2014, 111, E3614-23.

    21. Smith BC, Underbakke ES, Kulp DW, Schief WR, Marletta MA. “Nitric oxide synthase domain interfaces regulate electron transfer and calmodulin activation”. Proceedings of the National Academy of Sciences. 2013, 110, E3577-86.

    20. Underbakke ES, Surmeli NB, Smith BC, Wynia-Smith SL, Marletta MA. “Nitric oxide signaling”. Comprehensive Inorganic Chemistry II. 2013, Vol. 3, 241-262.

    19. Smith BC and Marletta MA. “Mechanisms of S-nitrosothiol formation and selectivity in nitric oxide signaling”. Current Opinion in Chemical Biology. 2012, 16, 498–506.

    18. Smith BC, Fernhoff NB, Marletta MA. “Mechanism and Kinetics of Inducible Nitric Oxide Synthase Auto-S-Nitrosation and Inactivation”. Biochemistry. 2012, 51, 1028–40.


    Graduate

    17. Smith BC, Anderson MA, Hoadley KA, Keck JL, Cleland WW, Denu JM. “Structural and Kinetic Isotope Effect Studies of Nicotinamidase (Pnc1) from Saccharomyces cerevisiae”. Biochemistry. 2012, 51, 243–56.

    16. Kasamatsu A, Nakao M, Smith BC, Comstock LR, Ono T, Kato J, Denu JM, Moss J. “Hydrolysis of O-Acetyl-ADP-ribose Isomers by ADP-ribosylhydrolase 3”. Journal of Biological Chemistry. 2011, 286, 21110–7.

    15. Hallows WC, Yu W, Smith BC, Devries MK, Ellinger JJ, Someya S, Shortreed MR, Prolla T, Markley JL, Smith LM, Zhao S, Guan KL, Denu JM. “Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction”. Molecular Cell. 2011, 41, 139–49.

    14. Smith BC, Settles B, Hallows WC, Craven MW, Denu JM. “SIRT3 substrate specificity determined by peptide arrays and machine learning”. ACS Chemical Biology. 2011, 6, 146–57. Appeared as the Cover Article

    13. Smith BC, Hallows WC, Denu JM. “A continuous microplate assay for sirtuins and nicotinamide-producing enzymes”. Analytical Biochemistry. 2009, 394, 101–9.

    12. Hallows WC, Smith BC, Lee S, Denu JM. “Ure(k)a! Sirtuins Regulate Mitochondria”. Cell. 2009, 137, 404–6.

    11. Smith BC and Denu JM. “Chemical mechanisms of histone lysine and arginine modifications”. Biochimica et Biophysica Acta. 2009, 1789, 45–57.

    10. Smith BC, Hallows WC, Denu JM. “Mechanisms and molecular probes of sirtuins”. Chemistry & Biology. 2008, 15, 1002–13.

    9. Smith BC and Denu JM. “Mechanism-based inhibition of Sir2 deacetylases by thioacetyl-lysine peptide”. Biochemistry. 2007, 46, 14478–86.

    8. Smith BC and Denu JM. “Acetyl-lysine analog peptides as mechanistic probes of protein deacetylases”. Journal of Biological Chemistry. 2007, 282, 37256–65.

    7. Garske AL, Smith BC, Denu JM. “Linking SIRT2 to Parkinson's disease”. ACS Chemical Biology. 2007, 2, 529–32.

    6. Smith BC and Denu JM. “Sir2 deacetylases exhibit nucleophilic participation of acetyl-lysine in NAD+ cleavage”. Journal of the American Chemical Society. 2007, 129, 5802–3.

    5. Smith BC and Denu JM. “Sirtuins caught in the act”. Structure. 2006, 14, 1207–8.

    4. Smith BC and Denu JM. “Sir2 Protein Deacetylases: Evidence for Chemical Intermediates and Functions of a Conserved Histidine”. Biochemistry. 2006, 45, 272–82.

    3. Grubisha O, Smith BC, Denu JM. “Small molecule regulation of Sir2 protein deacetylases”. FEBS Journal. 2005, 272, 4607–16.

    2. Borra MT, Smith BC, Denu JM. “Mechanism of human SIRT1 activation by resveratrol”. Journal of Biological Chemistry. 2005, 280, 17187–95.

    1. Schmidt MT, Smith BC, Jackson MD, Denu JM. “Coenzyme specificity of Sir2 protein deacetylases: implications for physiological regulation”. Journal of Biological Chemistry. 2004, 279, 40122–9.

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